Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0010200 (cough)
 23,843 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A case of itraconazole-induced hypokalemia with pulmonary aspergilloma is reported. A 68-year-old female who had been followed for rheumatoid arthritis, gastric ulcer and pulmonary aspergilloma was admitted to our hospital because of a cough, low grade fever and hemosputum. She was treated with itraconazole (100 mg/day) for pulmonary aspergilloma of the left upper lobe. Fifty seven days after starting the treatment, her serum potassium was 2.33 mEq/l. Since there was no history of diarrhea, vomiting or abuse of drugs known to cause hypokalemia, itraconazole- induced hypokalemia was suspected. Thirty one days after the discontinuation of the treatment with itraconazole, her serum potassium increased to 3.57 mEq/l without potassium supplement. The lymphocyte stimulation test for itraconazole was negative. This case suggests that serum potassium should be monitored in the patients treated with itraconazole.
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PMID:[A case of itraconazole-induced hypokalemia with pulmonary aspergilloma]. 858 96

Scorpion venoms contain specific toxins which block large conductance calcium-activated potassium (BKCa) channels. Use of these toxins has shown that a significant proportion of the action of bronchodilators such as beta-agonists, theophylline, and nitric oxide occurs as a result of the opening of BKCa channels. Similarly, these toxins have shown that inhibitors of airway neurotransmission also operate via BKCa channels. Drugs that open BKCa channels may be alternative bronchodilators (possibly "airway selective" and with fewer side effects) as well as inhibitors of pathophysiological neurogenic influences in asthma, chronic coughing and sneezing, and chronic bronchitis.
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PMID:Scorpion venoms: taking the sting out of lung disease. 871 88

Losartan potassium is an orally active, nonpeptide angiotensin II (AII) receptor antagonist. It is the first of a new class of drugs to be introduced for clinical use in hypertension. This novel agent binds competitively and selectively to the AII subtype 1 (AT(1)) receptor, thereby blocking AII-induced physiological effects. An active metabolite, E3174, contributes substantially to its antihypertensive effect, which persists throughout 24 hours after once-daily administration. In patients with mild to moderate hypertension, losartan potassium 50 to 100mg once daily as monotherapy lowers blood pressure to a similar degree to enalapril, atenolol and felodipine extended release (ER). Losartan potassium combined with hydrochlorothiazide reduces blood pressure further than either drug given separately. About one-third of patients with severe hypertension have responded to the combination product. Losartan potassium appears to be effective in elderly patients. Losartan potassium is very well tolerated. In clinical trials, dizziness was the only drug-related event reported more frequently with losartan potassium monotherapy than with placebo. First-dose hypotension is uncommon. An aspect of the drug's tolerability profile which may prove to be particularly advantageous is that it is associated with a similar incidence of cough to placebo in patients with a history of ACE inhibitor-related cough. Additionally, clinically relevant adverse metabolic effects or laboratory abnormalities have not been documented during losartan potassium therapy and renal function is preserved in patients with or without renal insufficiency. The adverse effect profile of the losartan potassium-hydrochlorothiazide combination resembles those for losartan potassium monotherapy and placebo. Long term tolerability data are limited (<2 years) but support the very good tolerability profile in shorter studies. Elements of the drug's profile yet to be assessed or reported fully in the literature include long term efficacy; potential to favourably influence cardiovascular and renovascular systems (and ultimately mortality) in patients with hypertension and, lastly, cost effectiveness and influence on quality of life. In summary, losartan potassium is the first AT(1)+ receptor antagonist to become available for the management of hypertension and, as such, it is an important new antihypertensive agent. Pending long term data as outlined above, it is likely to find initial use in patients with mild to severe hypertension who are unresponsive to, or intolerant of their current therapy. However, with its novel mechanism of action, good efficacy and favourable tolerability profile, losartan potassium is well placed to claim a prominent position in the management of patients with essential hypertension in the future.
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PMID:Losartan potassium: a review of its pharmacology, clinical efficacy and tolerability in the management of hypertension. 886 49

Angiotensin receptor antagonists represent a new class of drugs for the treatment of patients with hypertension. Reduction of blood pressure in patients with essential hypertension requires increased activity of the renin-angiotensin system. Losartan, the first orally active, nonpeptide angiotensin antagonist, specifically competes with angiotensin II (Ang II) for the AT1 receptor and reversibly alters the receptor. Maximum blood pressure reductions occur after doses of approximately 50 mg, although some patients will require 100 mg; the parent compound and a metabolite are responsible for a smooth 24-hour effect on blood pressure. Once-daily dosing with losartan has been documented to be safe. The drug's safety has been evaluated in 4,058 patients; of these patients, more than 1,200 were treated for longer than 6 months and more than 800 were treated for longer than 1 year with doses of 10 mg to 150 mg. Overall, no hypertensive patients were withdrawn from treatment because of elevated serum creatinine or potassium levels, and there were no reports of angioedema. In addition, some reductions in plasma uric acid levels were noted. Cough occurred significantly less often in patients treated with losartan than in those treated with hydrochlorothiazide or lisinopril. In contrast to angiotensin-converting enzyme (ACE) inhibitors, losartan does not activate bradykinin-nitric oxide-prostanoid vasodilation.
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PMID:Losartan: first of a new class of angiotensin antagonists for the management of hypertension. 893 38

Losartan potassium is the first of a new class of orally active antihypertensive drugs which antagonise the action of angiotensin (AT) II at the AT1 receptor subtype. Losartan potassium is converted by the liver to the active metabolite E-3174, which is a more potent antagonist at the AT1 receptor. E-3174 is responsible for most of the pharmacological effects of losartan potassium, and its long half-life contributes to the extended duration of action of the drug. Losartan potassium is effective as a once-daily antihypertensive agent. In mild to moderate hypertension, losartan potassium has similar efficacy to enalapril, atenolol and felodipine extended release. When losartan potassium is combined with hydrochlorothiazide there is a further reduction in blood pressure. Losartan potassium is well tolerated in mild, moderate and severe essential hypertension, with dizziness being reported as the only drug-related adverse effect. The overall rate of patient withdrawal from therapy due to adverse experiences with losartan potassium is lower (2.3%) than that of placebo (3.7%). First-dose hypotension is uncommon, perhaps due to the slower onset of action of the drug, and cough does not appear to be a significant problem. A number of areas concerning the safety and efficacy of losartan potassium remain to be clarified. In particular, long term tolerability studies are needed; cough only became apparent as an adverse effect of ACE inhibitors after 3 to 4 years of use. Postmarketing surveillance has shown that angioedema, a rare but life-threatening adverse effect of ACE inhibitors, also occurs with losartan potassium. Further data are needed on the use of losartan potassium in patients with renal impairment before accepting the recommendation that dosage adjustment is not necessary. The pharmacokinetics and pharmacodynamics of losartan potassium in patients with hepatic disease also require further investigation. Losartan potassium increases uric acid secretion and lowers plasma uric acid levels, which may be of benefit when losartan potassium is combined with a thiazide diuretic, but which may otherwise lead to uric acid stone formation and possibly to nephropathy. Simple control of blood pressure is no longer an adequate goal in the management of hypertension. Any new antihypertensive agent should also reduce cardiovascular events, prevent or cause regression of end-organ damage such as left ventricular hypertrophy, atherosclerosis and renal failure, and should not impair quality of life. Such data on losartan potassium are not currently available. Losartan potassium is likely to be used in patients who are intolerant of ACE inhibitors, but its future in the management of hypertension will depend on long term tolerability studies and data on its effects beyond simple blood pressure control.
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PMID:A risk-benefit assessment of losartan potassium in the treatment of hypertension. 901 Jun 43

Sensory nerves play an important role in airway disease by mediating central reflexes such as cough, and local axon reflexes resulting in the peripheral release of neuropeptides. We have tested whether the benzimidazolone compound, NS1619, an opener of large conductance calcium-activated potassium (BK Ca) channels, inhibits the activity of sensory fibers, and central and local airway reflexes in guinea pig airways. In in vitro single fiber recording experiments, NS1619 applied to identified receptive fields in the trachea inhibited the firing of A(delta)-fibers evoked by hypertonic saline and distilled water, and bradykinin-evoked firing of C-fibers. Electrically evoked nonadrenergic noncholinergic contractions of isolated bronchi mediated by the release of neurokinin A (NKA) from C-fibers, but not those elicited by exogenous NKA, were inhibited by NS1619. These effects of NS1619 were prevented by iberiotoxin, a selective blocker of BK Ca channels. In conscious guinea pigs, cough evoked by aerosolized citric acid was also inhibited by NS1619. These data show that BK Ca channel activation inhibits sensory nerve activity, resulting in a reduction of both afferent and efferent function. BK Ca channel openers may therefore be of potential benefit in reducing neurogenic inflammation and central reflexes seen during inflammatory conditions of the airways, and may represent a new class of antitussive drug.
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PMID:Activation of large conductance potassium channels inhibits the afferent and efferent function of airway sensory nerves in the guinea pig. 902 86

It is clear that there is still no definitive answer as to the role of RARs and C-fibres in cough, although the evidence would appear to implicate both fibre types, depending on the stimulus (Fig. 2). An upregulation of the activity of these fibres during disease states, by the action of inflammatory mediators, could contribute to an enhanced cough reflex, although the possible involvement of central sensitization provides another exciting possibility. Whilst an inhibition of the activity of airway afferents should conceivably lead to an inhibition of the cough reflex there remain few examples where this occurs. The available evidence suggests that agents such as opioids and cromoglycate can act on C-fibres, contributing to their antitussive activity, whilst frusemide has an inhibitory effect, on C- and A delta-fibres, only against certain stimuli. A more generalized inhibition of airway sensory nerves could be achieved by ion channel modulators, since these might act on both myelinated and non-myelinated fibres. It is interesting that the only clear examples of an inhibition of sensory nerve activity coupled with antitussive effects are provided by sodium channel blockers (local anaesthetics) and a potassium channel opener (NS1619). However, it should be borne in mind that cough is essentially a defensive reflex, becoming inappropriate during disease states. It might be desirable therefore to inhibit only the enhanced activity of sensory nerves seen during these conditions. Whether this is possible awaits further information on the changes in sensory nerve properties during inflammation.
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PMID:Modulation of cough and airway sensory fibres. 923 72

For the treatment of hypertension, the combination of an angiotensin-converting enzyme (ACE) inhibitor and a thiazide diuretic is supported by multiple lines of evidence, because these drugs have synergistic action and are expected to cancel out each other's adverse side effects. However, the long-term outcome of this combination antihypertensive therapy is not entirely clear. In the present multicenter open trial, we investigated the long-term efficacy and safety of combined antihypertensive therapy with an ACE inhibitor, lisinopril, and a thiazide diuretic, trichlormethiazide. A total of 466 patients with essential hypertension were treated with lisinopril alone (monotherapy group, n = 360) or with a combination of lisinopril with trichlormethiazide (combination therapy group, n = 106) for 1 year. The average blood pressure was effectively lowered to below 150/90 mmHg in both the monotherapy and the combination therapy groups throughout the study period. The average maintenance dose of lisinopril was lower when combined with thiazide than when given alone (9.8 vs. 11.5 mg/day, p < 0.001). Dry cough was the major side effect of lisinopril; no severe adverse effects were observed. The incidence of cough was not significantly different between the monotherapy group (13.1%) and the combination therapy group (11.3%). The increase in serum potassium observed in the monotherapy group was reversed by the concurrent use of the thiazide diuretic in the combination therapy group. Fasting blood glucose was significantly reduced in the monotherapy group; the reduction observed in the combination therapy group was not significant. Thus, the present results provide useful information as to the effectiveness and safety of combined antihypertensive therapy with lisinopril and a thiazide in comparison with monotherapy with lisinopril.
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PMID:Long-term evaluation of combined antihypertensive therapy with lisinopril and a thiazide diuretic in patients with essential hypertension. 948 36

Understanding the mechanism of action and the pharmacokinetic properties of vasodilatory drugs facilitates optimal use in clinical practice. It should be kept in mind that a drug belongs to a class but is a distinct entity, sometimes derived from a prototype to achieve a specific effect. The most common pharmacokinetic drug improvement is the development of a drug with a half-life sufficiently long to allow an adequate once-daily dosage. Developing a controlled release preparation can increase the apparent half-life of a drug. Altering the molecular structure may also increase the half-life of a prototype drug. Another desirable improvement is increasing the specificity of a drug, which may result in fewer adverse effects, or more efficacy at the target site. This is especially important for vasodilatory drugs which may be administered over decades for the treatment of hypertension, which usually does not interfere with subjective well-being. Compliance is greatly increased with once-daily dosing. Vasodilatory agents cause relaxation by either a decrease in cytoplasmic calcium, an increase in nitric oxide (NO) or by inhibiting myosin light chain kinase. They are divided into 9 classes: calcium antagonists, potassium channel openers, ACE inhibitors, angiotensin-II receptor antagonists, alpha-adrenergic and imidazole receptor antagonists, beta 1-adrenergic agonist, phosphodiesterase inhibitors, eicosanoids and NO donors. Despite chemical differences, the pharmacokinetic properties of calcium antagonists are similar. Absorption from the gastrointestinal tract is high, with all substances undergoing considerable first-pass metabolism by the liver, resulting in low bioavailability and pronounced individual variation in pharmacokinetics. Renal impairment has little effect on pharmacokinetics since renal elimination of these agents is minimal. Except for the newer drugs of the dihydropyridine type, amlodipine, felodipine, isradipine, nilvadipine, nisoldipine and nitrendipine, the half-life of calcium antagonists is short. Maintaining an effective drug concentration for the remainder of these agents requires multiple daily dosing, in some cases even with controlled release formulations. However, a coat-core preparation of nifedipine has been developed to allow once-daily administration. Adverse effects are directly correlated to the potency of the individual calcium antagonists. Treatment with the potassium channel opener minoxidil is reserved for patients with moderately severe to severe hypertension which is refractory to other treatment. Diazoxide and hydralazine are chiefly used to treat severe hypertensive emergencies, primary pulmonary and malignant hypertension and in severe preeclampsia. ACE inhibitors prevent conversion of angiotensin-I to angiotensin-II and are most effective when renin production is increased. Since ACE is identical to kininase-II, which inactivates the potent endogenous vasodilator bradykinin, ACE inhibition causes a reduction in bradykinin degradation. ACE inhibitors exert cardioprotective and cardioreparative effects by preventing and reversing cardiac fibrosis and ventricular hypertrophy in animal models. The predominant elimination pathway of most ACE inhibitors is via renal excretion. Therefore, renal impairment is associated with reduced elimination and a dosage reduction of 25 to 50% is recommended in patients with moderate to severe renal impairment. Separating angiotensin-II inhibition from bradykinin potentiation has been the goal in developing angiotensin-II receptor antagonists. The incidence of adverse effects of such an agent, losartan, is comparable to that encountered with placebo treatment, and the troublesome cough associated with ACE inhibitors is absent.
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PMID:Clinical pharmacokinetics of vasodilators. Part I. 964 8

We describe a 28-year-old subject employed as a roofer in a construction company since the age of 19, who developed work-related symptoms of a cough, shortness of breath, wheezing, rhinitis and headaches. A description of a usual day at work suggested that the symptoms worsened while he was sawing corrugated fiber cement. Baseline spirometry was normal, and there was a mild bronchial hyperresponsiveness to carbachol. A skin patch test to chromium was negative. A specific inhalation challenge showed a boderline fall in forced expiratory volume in 1 s (FEV1) after exposure to fiber cement dust. Exposure to nebulization of potassium dichromate (K2Cr2O7), at 0.1 mg.ml-1 for 30 min, was followed by an immediate fall by 20% FEV1. Simultaneously, a significant increase in bronchial hyperresponsiveness was demonstrated.
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PMID:Occupational asthma due to chromium. 978 25


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